1. Field of the Invention
This invention relates to stents provided with coatings for eluting medication to prevent or lessen the severity of restenosis.
2. Prior Art
In order to minimize the response of surrounding tissue to the trauma of stent insertion and expansion, stent coatings must be biocompatible. A further requirement is that a stent coating must adhere to a substrate undergoing plastic deformation. This occurs during insertion and expansion of the stent into the vasculature system. Plastic deformation involves grain rotation and elongation, and intersection of slip planes with the substrate surface. The result is that on a scale below the grain size of the substrate, deformation is highly non-uniform, with some areas undergoing little or no deformation and others extreme deformation with associated increase in surface roughness and irregularity. Therefore, coating adhesion must be preserved through the deformation process.
Conventional stent coatings can be classified as being either passive or active. Passive coatings rely on biocompatible materials to minimize the body's response to placement of the stent into the vasculature. Generally recognized “passive” coating materials include carbon, iridium oxide, titanium, and the like, as disclosed in U.S. Pat. No. 5,824,056 to Rosenberg. U.S. Pat. No. 5,649,951 to Davidson discloses coatings of zirconium oxide or zirconium nitride.
Drug eluting or “active” coatings have proven more effective for the prevention of restenosis. Such stents generally comprise a surface polymer containing a therapeutic drug for timed release. A second coating may be added to extend the period of effectiveness by limiting the rate of drug diffusion from the first, drug-containing coating. This second coating may be a polymer, or a sputtered coating as described in U.S. Pat. No. 6,716,444 to Castro et al.
However, polymeric drug eluting coatings suffer from a number of disadvantages. First, they can have poor adhesion to the stent, especially while undergoing plastic deformation during insertion and expansion of the stent into the vasculature. Secondly, due to biocompatibility/hemocompatibility issues some polymers actually contribute to restenosis. Finally, that part of the coating facing the inside of the vasculature lumen loses its medication content to the bloodstream with little beneficial effect.
U.S. Pat. No. 6,805,898 to Wu et al. attempted to overcome adhesion problems by introducing roughness to the vasculature-facing portion of the stent while leaving the blood-facing side in a polished condition for better hemocompatibility. Surface roughness was increased by means of grit blasting, sputtering, and the like. Not only did augmenting surface roughness improve adhesion between the polymer and the stent, it also allowed for a thicker polymer coating to be applied. However, the final stent configuration still had eluting polymer in contact with body tissue, allowing biocompatibility issues to persist.
U.S. Pat. No. 5,607,463 to Schwartz et al. carried out experiments in which it was shown that tissue response to polymers could be reduced by means of a barrier layer of tantalum and niobium thin films on the exposed polymer surfaces. Specifically, in vivo tests showed an absence of thrombosis, inflammatory response, or neointimal proliferation when a thin tantalum or niobium barrier layer covered a polymer. However, in the case of a drug eluting polymer, these coatings detrimentally isolated the drug from the tissue as well.
U.S. Patent Application Pub. No. 2004/0172124 to Vallana et al. optimized the coating configuration by limiting the drug-eluting material to only that portion of the stent surface in contact with the vasculature. This was done by confining the drug eluting polymer to outward facing channels which were micro-machined into the stent mesh elements. All other stent surfaces were coated with hemocompatible carbon. Thus, the use of a biocompatible-problematic carrier polymer was minimized, but not eliminated.
In addition, U.S. Pat. No. 6,820,676 to Palmaz shows that, independent of the stent's surface composition, the surface texture of the stent or coating has an effect on the ability of proteins to adsorb into the stent surface, ultimately allowing thrombosis formation. It was shown that the surface texture can be controlled by grain size and other means to prevent protein adsorption and subsequent thrombosis.
Thus, even though much work has been done to develop stent systems comprising drug eluting polymers while minimizing, and even eliminating, thrombosis, inflammatory response and neointimal proliferation, further improvements are required to fully realize these goals. The present stent coating is believed to accomplish just that.